Potential anticonvulsive properties of endogenous prostaglandins formed in mouse brain.
The levels of 5 different prostanoids (PGD2, PGF2 alpha, PGE2, TXB2 and 6-keto-PGF1 alpha) formed in whole mouse brain in vivo were measured by specific radioimmunoassays. Basal concentrations were found to be very low (few ng/g wet weight). A marKed increase occurred during convulsions induced by either pentylenetetrazole or by electroconvulsive shock. Under both conditions the major cyclooxygenase product detected was PGD2, followed by PGF2 alpha and lower concentrations of the other prostanoids. The non-steroidal anti-inflammatory drugs flurbiprofen, indomethacin, and diclofenac dose-dependently inhibited the pentylenetetrazole-induced formation of prostaglandins. Concomitantly these 3 compounds dose-dependently increased the acute toxicity of pentylenetetrazole (decrease in LD50). Conversely, if levels of cerebral prostaglandins were enhanced by a preceding electroshock, the toxicity of pentylenetetrazole was significantly reduced (increase in LD50), and the time of onset of clonic seizures was markedly prolonged. Both the effect on the latency time and the LD50 could be reversed if the cerebral prostaglandin synthesis was prevented by indomethacin, or if the time interval between the electroshock and pentylenetetrazole administration was extended, so that the electroshock-stimulated prostaglandin concentrations had declined to basal levels again. These findings indicate that endogenous prostanoids formed in mouse brain during convulsions might possess anticonvulsive properties.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004008:Diclofenac / Q000494:pharmacology; D004597:Electroshock; D005480:Flurbiprofen / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010433:Pentylenetetrazole / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis*
D011453:Prostaglandins; D004008:Diclofenac; D005480:Flurbiprofen; D011451:Prostaglandin-Endoperoxide Synthases; D010433:Pentylenetetrazole; D007213:Indomethacin